Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19.

BACKGROUND: Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19). OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival. DESIGN: In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated. A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival. A Cox model with inverse probability weighting to adjust for confounding was used. SETTING: 67 hospitals in the United States. PARTICIPANTS: Adults with COVID-19 admitted to a participating ICU. MEASUREMENTS: Time to death, censored at hospital discharge, or date of last follow-up. RESULTS: Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men. A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event. Independent predictors of VTE were male sex and higher D-dimer level on ICU admission. Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation. In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]). LIMITATION: Observational design. CONCLUSION: Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation. PRIMARY FUNDING SOURCE: None.

AKI Treated with Renal Replacement Therapy in Critically Ill Patients with COVID-19.

BACKGROUND: AKI is a common sequela of coronavirus disease 2019 (COVID-19). However, few studies have focused on AKI treated with RRT (AKI-RRT). METHODS: We conducted a multicenter cohort study of 3099 critically ill adults with COVID-19 admitted to intensive care units (ICUs) at 67 hospitals across the United States. We used multivariable logistic regression to identify patient-and hospital-level risk factors for AKI-RRT and to examine risk factors for 28-day mortality among such patients. RESULTS: A total of 637 of 3099 patients (20.6%) developed AKI-RRT within 14 days of ICU admission, 350 of whom (54.9%) died within 28 days of ICU admission. Patient-level risk factors for AKI-RRT included CKD, men, non-White race, hypertension, diabetes mellitus, higher body mass index, higher d-dimer, and greater severity of hypoxemia on ICU admission. Predictors of 28-day mortality in patients with AKI-RRT were older age, severe oliguria, and admission to a hospital with fewer ICU beds or one with greater regional density of COVID-19. At the end of a median follow-up of 17 days (range, 1-123 days), 403 of the 637 patients (63.3%) with AKI-RRT had died, 216 (33.9%) were discharged, and 18 (2.8%) remained hospitalized. Of the 216 patients discharged, 73 (33.8%) remained RRT dependent at discharge, and 39 (18.1%) remained RRT dependent 60 days after ICU admission. CONCLUSIONS: AKI-RRT is common among critically ill patients with COVID-19 and is associated with a hospital mortality rate of >60%. Among those who survive to discharge, one in three still depends on RRT at discharge, and one in six remains RRT dependent 60 days after ICU admission.

Practice patterns in transitioning patients from chronic kidney disease to dialysis: a survey of United States nephrologists.

BACKGROUND: There are no guidelines for transitioning patients from chronic kidney disease stage 5 to hemodialysis. We conducted this study to determine if there are uniform patterns in how nephrologists transition patients to dialysis. METHODS: We designed an electronic survey with 39 questions and sent it to a database of practicing nephrologists at the National Kidney Foundation. Factors that were important for transitioning a patient to hemodialysis were evaluated, including medication changes on dialysis initiation, dry weight and dialysis prescription. RESULTS: 160 US Nephrologists replied to the survey; 18% (29/160) of the responses were completed via social media sites. Prior to dialysis, 74% (118/160), prescribed furosemide and 67% (107/160) used furosemide with metolazone. Once dialysis started, only 46% (74/160) of the responders continued patients on diuretics daily. Hypertension medications prescribed in dialysis were calcium channel blockers 69% (112/160), beta blockers 36% (58/160), angiotensin converting enzyme inhibitor 32% (53/160), angiotensin receptor blocker 29% (46/160) and diuretics 25% (42/160). Once dialysis started, 68% (109/160) routinely changed medications. Most, 67% (107/160) ordered patients to avoid anti-hypertensive medications on dialysis days to allow for ultrafiltration. Dry weight was determined in the first week by 29% (46/160) and in the first month by 53% (85/160). Most, 59% (94/160) felt that multiple causes lead to hypertension. Most nephrologists would prescribe small dialyzers and a shorter period of time for the first dialysis session. CONCLUSION: The transition period to chronic hemodialysis has variations in practice patterns and may benefit from further studies to optimize clinical practice.

Dialysis in the Elderly and Impact of Institutionalization in the United States Renal Data System.

BACKGROUND: We hypothesized that in the very elderly dialysis patients in the United States, institutionalization in nursing homes would increase mortality in addition to age alone. METHODS: Incident dialysis patients from 2001 to 2008 above the age of 70 were included. Patients above 70 were categorized into 4 groups according to age as 70-75, 76-80, 81-85, and >85 years and further divided into institutionalized and noninstitutionalized. Kaplan-Meier survival curves were plotted to assess patient survival. RESULTS: A total of 349,440 patients were identified above the age of 70 at the time of initiation of dialysis. For institutionalized patients, the mean survival was significantly lower, 1.71 ± 0.03 years for those in the age range 70-75, 1.44 ± 0.02 years for those in the age range 76-80, 1.25 ± 0.02 years for those in the age range 81-85, and 1.04 ± 0.02 for those in the >85 years age group (p = 0.0001). The hazard ratio for mortality in institutionalized elderly patients on dialysis was 1.80 ([95% CI 1.77-1.83]; p = 0.0001). After adjustment for other variables (multivariate Cox regression), to be institutionalized was still an independent risk factor for mortality (adjusted hazard ratio = 1.57 [95% CI 1.54-1.60]; p = 0.0001). CONCLUSION: There was increased mortality in institutionalized elderly patients as compared to noninstutionalized elderly patients in the same age group. In accordance with the increased frailty and decreased benefits of therapies in the very elderly, especially in those with additional co-morbidities besides age, palliative and end-of-life care should be considered.

What Do We Know about Opioids and the Kidney?

Evidence suggests a link between opioid use and kidney disease. This review summarizes the known renal manifestations of opioid use including its role in acute and chronic kidney injury. Both the direct and indirect effects of the drug, and the context which leads to the development of renal failure, are explored. While commonly used safely for pain control and anesthesia in those with kidney disease, the concerns with respect to side effects and toxicity of opioids are addressed. This is especially relevant with the worldwide increase in the use of opioids for medical and recreational use.

Towards Optimal Cardiovascular Health: A Comprehensive Review of Preventive Strategies.

Heart disease remains a prominent global health concern, with cardiovascular disease (CVD) standing as a leading cause of death worldwide. Preventing heart disease not only decreases the risk of premature death but also mitigates complications like heart attacks, strokes, and arrhythmias, thereby enhancing overall health and quality of life. The economic burden of heart disease treatment highlights the importance of implementing preventive measures, such as lifestyle changes and early interventions, which can alleviate healthcare costs. These strategies, targeting risk factors like hypertension (HTN), diabetes mellitus (DM), dyslipidemia, and obesity, not only prevent heart disease but also reduce the risk of other health issues. Herein, this review covers various preventive measures, including dietary interventions, exercise, controlling HTN, DM, cholesterol, and weight, smoking cessation, and pharmacological interventions. By critically analyzing the guidelines and leveraging robust data alongside variations in recommendations, this review aims to elucidate effective primary prevention strategies for CVD.

A Rare Case of Congestive Heart Failure due to Isolated Aortic Valve Disease in a Middle-Aged Man Secondary to Rheumatic Fever.

Rheumatic heart disease (RHD) is commonly seen in people from developing and low-income countries. More cases are being recorded in developed countries due to migration and globalization. RHD develops in people with a history of rheumatic fever; it is an autoimmune response to group A streptococcal infection due to similarities at the molecular level. Congestive heart failure, arrhythmia, atrial fibrillation, stroke, and infective endocarditis are a few of the many complications associated with RHD. Here we present a case of a 48-year-old male with a past medical history of rheumatic fever at the age of 12 years, who presented to the emergency room (ER) complaining of bilateral ankle swelling, dyspnea on exertion, and palpitations. The patient was tachycardic with a heart rate of 146 beats per minute and tachypneic with a respiratory rate of 22 breaths per minute. On physical exam, there was a harsh systolic and diastolic murmur at the right upper sternal border. A 12-lead electrocardiogram (EKG) revealed atrial flutter with a variable block. Chest X-ray revealed an enlarged cardiac silhouette with a pro-brain natriuretic peptide (proBNP) of 2,772 pg/mL (normal ≤ 125 pg/mL). The patient was stabilized with metoprolol and furosemide and was admitted to the hospital for further investigation. Transthoracic echocardiogram showed left ventricular ejection fraction (LVEF) of 50-55% with severe concentric hypertrophy of the left ventricle with a severely dilated left atrium. Increased thickness of the aortic valve with severe stenosis and a peak gradient of 139 mm Hg and a mean gradient of 82 mm Hg was noted. The valve area was measured to be 0.8 cm2. Transesophageal echocardiogram showed a tri-leaflet aortic valve with commissural fusion of valve cusps with severe leaflet thickening consistent with rheumatic valve disease. The patient underwent tissue aortic valve replacement with a bioprosthetic valve. The pathology report showed extensive fibrosis and calcification of the aortic valve. The patient came in for a follow-up visit 6 months later and expressed feeling better and more active.

Peritoneal dialysis should not be the first choice for renal replacement therapy in the elderly.

Based on our review, it appears fair to infer that substantive differences in long-term outcome with PD compared with in-center HD have not been documented. PD may offer a slight advantage in younger, nondiabetic patients in the early phase of renal replacement therapy. Nevertheless, PD is not an advantageous option for that large cohort of the dialysis population in the United States comprised of elderly patients with diabetes.

A Case of Acute Colonic Pseudo-Obstruction (Ogilvie's Syndrome) in a Nonsurgical Patient with Plasma Cell Leukemia.

Ogilvie's syndrome, also known as acute colonic pseudo-obstruction (ACPO), is a rare, nonobstructive dilation of the colon of unclear etiology. We present the case of a patient who presented with Ogilvie's syndrome and significant hypokalemia due to colonic loss despite repletion. This case report demonstrates the difficulty in diagnosis, treatment, and outcome.

Clotting of Hemodialysis Access in Patients with COVID-19 in an Inner-City Hospital.

BACKGROUND: An increased incidence of thrombotic complications in patients with coronavirus disease 2019 (COVID-19) has been reported. Severe acute kidney injury (AKI) is one of the major clinical manifestations of COVID-19 with the need for renal replacement therapy. It was observed that hemodialysis (HD) accesses tended to thrombose more often in the COVID-19 population than in non-COVID-19 patients. We hypothesize that the hypercoagulable state of COVID-19 is associated with higher incidence of access clotting. METHOD: In this retrospective single-centered study at Kings County Hospital in New York City, 1,075 patients with COVID-19 were screened, and 174 patients who received HD from January 3, 2021 to May 15, 2020 were enrolled to examine the risk factors of dialysis access clotting in patients with COVID-19. RESULTS: Of the 174 patients, 109 (63%) were COVID-19 positive. 39 (22.6%) patients had dialysis access clotting at least once during their hospitalization, and they had significantly higher body mass index (BMI) (p = 0.001), higher rates of COVID-19 (p = 0.015), AKI (p < 0.001), higher platelet counts (p = 0.029), higher lactate dehydrogenase levels (p = 0.009), and lower albumin levels (p = 0.001) than those without access malfunctions. Low albumin levels (p = 0.008), AKI (p = 0.008), and high BMI (p = 0.018) were risk factors associated with HD access clotting among COVID-19 patients. CONCLUSION: Patients with COVID-19 who receive HD for AKI with high BMI are at a higher risk of clotting their HD access.

Opioids and Acute Kidney Injury.

Opioid use and misuse in the United States has been at epidemic proportions and is predicted to increase further in the setting of the Coronavirus disease 19 pandemic. Acute kidney injury is a condition associated with significant morbidity and increased mortality. We review the literature on the effect of opioids on kidney function and critically examine the association between opioid use and acute kidney injury and identify at-risk populations in whom opioids should be used with caution. We also discuss the role of biomarkers in elucidating this condition and propose preventive measures, novel therapeutic options, and research directions.

COVID-19 Pneumonia Precipitating Acute Anterior Wall Myocardial Infarction With Large Left Ventricular Apical Thrombus.

Initial reports suggest an increased thrombotic risk in coronavirus disease 2019 (COVID-19). We present a case of COVID-19 pneumonia that precipitated chest pain, an acute anterior wall ST-elevation myocardial infarction on the fifth day of hospitalization resulting in large left ventricular apical thrombus.

Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19.

Importance: Therapies that improve survival in critically ill patients with coronavirus disease 2019 (COVID-19) are needed. Tocilizumab, a monoclonal antibody against the interleukin 6 receptor, may counteract the inflammatory cytokine release syndrome in patients with severe COVID-19 illness. Objective: To test whether tocilizumab decreases mortality in this population. Design, Setting, and Participants: The data for this study were derived from a multicenter cohort study of 4485 adults with COVID-19 admitted to participating intensive care units (ICUs) at 68 hospitals across the US from March 4 to May 10, 2020. Critically ill adults with COVID-19 were categorized according to whether they received or did not receive tocilizumab in the first 2 days of admission to the ICU. Data were collected retrospectively until June 12, 2020. A Cox regression model with inverse probability weighting was used to adjust for confounding. Exposures: Treatment with tocilizumab in the first 2 days of ICU admission. Main Outcomes and Measures: Time to death, compared via hazard ratios (HRs), and 30-day mortality, compared via risk differences. Results: Among the 3924 patients included in the analysis (2464 male [62.8%]; median age, 62 [interquartile range {IQR}, 52-71] years), 433 (11.0%) received tocilizumab in the first 2 days of ICU admission. Patients treated with tocilizumab were younger (median age, 58 [IQR, 48-65] vs 63 [IQR, 52-72] years) and had a higher prevalence of hypoxemia on ICU admission (205 of 433 [47.3%] vs 1322 of 3491 [37.9%] with mechanical ventilation and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of <200 mm Hg) than patients not treated with tocilizumab. After applying inverse probability weighting, baseline and severity-of-illness characteristics were well balanced between groups. A total of 1544 patients (39.3%) died, including 125 (28.9%) treated with tocilizumab and 1419 (40.6%) not treated with tocilizumab. In the primary analysis, during a median follow-up of 27 (IQR, 14-37) days, patients treated with tocilizumab had a lower risk of death compared with those not treated with tocilizumab (HR, 0.71; 95% CI, 0.56-0.92). The estimated 30-day mortality was 27.5% (95% CI, 21.2%-33.8%) in the tocilizumab-treated patients and 37.1% (95% CI, 35.5%-38.7%) in the non-tocilizumab-treated patients (risk difference, 9.6%; 95% CI, 3.1%-16.0%). Conclusions and Relevance: Among critically ill patients with COVID-19 in this cohort study, the risk of in-hospital mortality in this study was lower in patients treated with tocilizumab in the first 2 days of ICU admission compared with patients whose treatment did not include early use of tocilizumab. However, the findings may be susceptible to unmeasured confounding, and further research from randomized clinical trials is needed.

A review of big data and medical research.

Universally, the volume of data has increased, with the collection rate doubling every 40 months, since the 1980s. "Big data" is a term that was introduced in the 1990s to include data sets too large to be used with common software. Medicine is a major field predicted to increase the use of big data in 2025. Big data in medicine may be used by commercial, academic, government, and public sectors. It includes biologic, biometric, and electronic health data. Examples of biologic data include biobanks; biometric data may have individual wellness data from devices; electronic health data include the medical record; and other data demographics and images. Big data has also contributed to the changes in the research methodology. Changes in the clinical research paradigm has been fueled by large-scale biological data harvesting (biobanks), which is developed, analyzed, and managed by cheaper computing technology (big data), supported by greater flexibility in study design (real-world data) and the relationships between industry, government regulators, and academics. Cultural changes along with easy access to information via the Internet facilitate ease of participation by more people. Current needs demand quick answers which may be supplied by big data, biobanks, and changes in flexibility in study design. Big data can reveal health patterns, and promises to provide solutions that have previously been out of society's grasp; however, the murkiness of international laws, questions of data ownership, public ignorance, and privacy and security concerns are slowing down the progress that could otherwise be achieved by the use of big data. The goal of this descriptive review is to create awareness of the ramifications for big data and to encourage readers that this trend is positive and will likely lead to better clinical solutions, but, caution must be exercised to reduce harm.

In-hospital cardiac arrest in critically ill patients with covid-19: multicenter cohort study.

OBJECTIVES: To estimate the incidence, risk factors, and outcomes associated with in-hospital cardiac arrest and cardiopulmonary resuscitation in critically ill adults with coronavirus disease 2019 (covid-19). DESIGN: Multicenter cohort study. SETTING: Intensive care units at 68 geographically diverse hospitals across the United States. PARTICIPANTS: Critically ill adults (age ≥18 years) with laboratory confirmed covid-19. MAIN OUTCOME MEASURES: In-hospital cardiac arrest within 14 days of admission to an intensive care unit and in-hospital mortality. RESULTS: Among 5019 critically ill patients with covid-19, 14.0% (701/5019) had in-hospital cardiac arrest, 57.1% (400/701) of whom received cardiopulmonary resuscitation. Patients who had in-hospital cardiac arrest were older (mean age 63 (standard deviation 14) v 60 (15) years), had more comorbidities, and were more likely to be admitted to a hospital with a smaller number of intensive care unit beds compared with those who did not have in-hospital cardiac arrest. Patients who received cardiopulmonary resuscitation were younger than those who did not (mean age 61 (standard deviation 14) v 67 (14) years). The most common rhythms at the time of cardiopulmonary resuscitation were pulseless electrical activity (49.8%, 199/400) and asystole (23.8%, 95/400). 48 of the 400 patients (12.0%) who received cardiopulmonary resuscitation survived to hospital discharge, and only 7.0% (28/400) survived to hospital discharge with normal or mildly impaired neurological status. Survival to hospital discharge differed by age, with 21.2% (11/52) of patients younger than 45 years surviving compared with 2.9% (1/34) of those aged 80 or older. CONCLUSIONS: Cardiac arrest is common in critically ill patients with covid-19 and is associated with poor survival, particularly among older patients.

Atypical Causes of Urinary Tract Obstruction.

Acute kidney injury due to urinary tract obstruction invariably suggests lower urinary tract obstruction or bilateral ureteric obstruction since obstruction of a single kidney while the contralateral kidney is normal and not obstructed would not cause a perceptible rise in creatinine. Assuming a total body volume of 42 L, 70 kg male that generates approximately 1400 mg of creatinine daily (20 mg/kg/day) who has complete urinary tract obstruction would experience a 3.33 mg/dL per day increase in serum creatinine. Thus, for an individual who had prior normal renal function and who presents with a creatinine of 30 mg/dL, one could surmise that the obstructive pathology had lasted at least 10 days. However, the rise in serum creatinine is a poor marker of renal injury and subsequent prognosis. Urinary tract obstruction leading to AKI can be due to a variety of causes, and its management is tailored to the underlying etiology. This case series describes the varied clinical course of four patients at our center who experienced AKI from atypical causes of obstructive uropathy. Current and future diagnostic modalities and caveats in the treatment of this disease entity are also discussed.

Convulsive Syncope Induced by Ventricular Arrhythmia Masquerading as Epileptic Seizures: Case Report and Literature Review.

It is important but difficult to distinguish convulsive syncope from epileptic seizure in many patients. We report a case of a man who presented to emergency department after several witnessed seizure-like episodes. He had a previous medical history of systolic heart failure and automated implantable converter defibrillator (AICD) in situ. The differential diagnoses raised were epileptic seizures and convulsive syncope secondary to cardiac arrhythmia. Subsequent AICD interrogation revealed ventricular tachycardia and fibrillation (v-tach/fib). Since convulsive syncope and epileptic seizure share many similar clinical features, early diagnosis is critical for choosing the appropriate management and preventing sudden cardiac death in patients with presumed epileptic seizure.

Rhabdomyolysis and Acute Kidney Injury Requiring Dialysis as a Result of Concomitant Use of Atypical Neuroleptics and Synthetic Cannabinoids.

The use of synthetic cannabinoids (SCBs) is associated with many severe adverse effects that are not observed with marijuana use. We report a unique case of a patient who developed rhabdomyolysis and acute kidney injury (AKI) requiring dialysis after use of SCBs combined with quetiapine. Causes for the different adverse effects profile between SCBs and marijuana are not defined yet. Cases reported in literature with SCBs use have been associated with reversible AKI characterized by acute tubular necrosis and interstitial nephritis. Recent studies have showed the involvement of cytochromes P450s (CYPs) in biotransformation of SCBs. The use of quetiapine which is a substrate of the CYP3A4 and is excreted (73%) as urine metabolites may worsen the side effect profiles of both quetiapine and K2. SCBs use should be included in the differential diagnosis of AKI and serum Creatinine Phosphokinase (CPK) level should be monitored. Further research is needed to identify the mechanism of SCBs nephrotoxicity.

Parameters used to discontinue dialysis in acute kidney injury recovery: a survey of United States nephrologists.

BACKGROUND: Despite advances in the approach to cure acute kidney injury (AKI), including definition, classification and treatment methods, there are no standard criteria to withdraw dialysis in the setting of improving AKI. We conducted this survey to elucidate parameters that United States (US) nephrologists used to determine when to stop dialysis with improving renal function in AKI. We hypothesized that there would be a difference in approach to weaning a patient off dialysis based on years in practice or the number of cases of AKI treated per year. METHODS: This was an anonymous electronic survey of practicing nephrologists who treated AKI. Data was de-identified and analyzed using descriptive statistics. RESULTS: The commonest criteria used to stop dialysis when renal function improved was, in decreasing order of importance, resolution in oliguria (51%), resolution of volume overload (29%), improvement in serum creatinine (26.7%) and resolution of hyperkalemia (21%). The most common reasons for re-starting dialysis within 28 days did not show a specific trend but respondents (20%) reported re-starting if estimated glomerular filtration rates (eGFR) declined. There was no significant pattern in approach to withdrawing dialysis or resuming dialysis based on the number of years in nephrology practice. However, responses of nephrologists who saw more than 20 AKI patients/year were significantly different in stopping dialysis with clinical stabilization of blood pressure (p < 0.001), improvement in respiratory parameters (p = 0.005), improvement in pre-dialysis blood urea nitrogen (BUN) levels despite the same dose of dialysis (p = 0.05) and resolution of oliguria (p = 0.025) compared to those who saw fewer cases. CONCLUSION: Resolution of oliguria was the commonest factor used to help deciding to stop dialysis in improving AKI. However, considerable variation was noted among US nephrologists who participated in this survey, regarding what criteria they used to withdraw dialysis in the setting of improving AKI. These results call for more studies in withdrawing dialysis in the setting of AKI that could lead to guideline formulation.

Chronic kidney disease in the elderly: evaluation and management.

Chronic kidney disease (CKD) is a very common clinical problem in elderly patients and is associated with increased morbidity and mortality. As life expectancy continues to improve worldwide, there is a rising prevalence of comorbidities and risk factors such as hypertension and diabetes predisposing to a high burden of CKD in this population. The body of knowledge on the approach to elderly patient with CKD is still evolving. Thus, this review seeks to explore the epidemiology and to discuss current understanding of challenges in the diagnosis and management of elderly patients CKD.